The first 2 authors contributed equally to this article.
Serum cell-free DNA in renal cell carcinoma†
A diagnostic and prognostic marker
Article first published online: 28 JUN 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 1, pages 82–90, 1 January 2012
How to Cite
de Martino, M., Klatte, T., Haitel, A. and Marberger, M. (2012), Serum cell-free DNA in renal cell carcinoma. Cancer, 118: 82–90. doi: 10.1002/cncr.26254
- Issue published online: 16 DEC 2011
- Article first published online: 28 JUN 2011
- Manuscript Accepted: 13 APR 2011
- Manuscript Revised: 10 APR 2011
- Manuscript Received: 14 MAR 2011
- renal cell carcinoma;
- cell-free DNA;
- receiver operating characteristic curve
Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell-free DNA.
Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real-time polymerase chain reaction was used to assess total cell-free DNA (ring finger protein 185 [RNF185]) and CpG island methylation of Ras association domain family member 1A (RASSF1A) von Hippel-Lindau (VHL), prostaglandin-endoperoxidase synthase 2 (PTGS2), and P16 (cyclin-dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific survival were evaluated.
Total cell-free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes (P = .007). Total cell-free DNA levels were higher in patients with metastatic RCC (P < .001) and necrotic RCC (P = .003) and were associated with poorer disease-specific survival (P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score (P < .001) and categorized total cell-free DNA levels (P = .028) were retained as independent prognostic factors.
The current results indicated that cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell-free DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;. © 2011 American Cancer Society.